The present invention relates to an optical measurement system for the determination of transmitted radiation and scattered radiation in a liquid sample contained in a capillary tube and subject to measurement radiation, where the axis of the beam of measurement radiation is essentially at a right angle to the axis of the capillary tube, and where a first detector which is used for picking up transmitted radiation, is positioned in an area near the axis of the beam of measurement radiation, and where a second detector which is used for picking up scattered radiation, is placed at a certain distance from the first detector in the direction of the axis of the capillary tube.
Such measurement systems are predominantely used for testing liquid media containing absorbent scattering particles, e.g., whole blood samples and other organic or inorganic liquids, but also liquid samples in environmental technology, such as waste-water samples.
The determination of the concentration of substances in such liquids may be effected by measuring absorption at various wavelengths in a transmission configuration and in a scattered light configuration, where the measured intensities of transmitted and scattered light together with calibrating data from known samples and zero values (measured values when the capillary is filled with pure water) permit the substance concentrations to be determined.
From EP 0 800 074 A1 a device is known for the determination of the concentration of derivatives of hemoglobin in an undiluted, unhemolised whole blood sample. The whole blood sample contained in a test tube is subjected to measurement radiation that is made up of at least n monochromatic, narrowband components of various wavelengths. A first detector unit is positioned on the axis of the primary beam (transmission geometry). The detector has a relatively small beam entry area and essentially picks up radiation from the central beam. In a second measurement position, at a certain angle with the axis of the primary beam, a second detector unit is placed for picking up scattered radiation. Both detector units are connected via signal lines to an evaluation unit, where values for the hemoglobin derivatives are computed by means of a stored calibration matrix.
From EP 0 720 013 A2 a method and device for the optical determination of blood parameters is known, where one embodiment shows a flow cell in a housing, which takes up the blood sample. Measurement radiation from a lightsource is introduced at a right angle to the axis of the flow cell, and on the other side of the cell a first detector is positoned in transmission configuration, while further detectors are provided in scatter configuration at various distances from the first. The measuring cell of the embodiment described may be directly included in an extracorporeal blood circuit and thus be used in the optimisation of a dialysis process.
Furthermore, in U.S. Pat. No. 4,745,279 a device for hematocrit-measurement in blood has been described, where infrared radiation is radiated into a transparent cell through which blood flows. A first detector situated at the bottom of the cell picks up diffusely scattered light from the sample, which presents a measure for oxygen saturation. A second detector placed on a sidewall of the cell is used for measuring hematocrit. Excitation light for both detectors is provided by two different lightsources (LEDs), which are placed pairwise in the respective regions of the detectors. A third lightsource, which does not interact with the sample, and a third detector are used to create a reference signal.
A measurement system of the kind described above is known from EP 0 575 712 A2, which may be used to simultaneously determine the hematocrit value and one other quantity, for instance sodium concentration, directly in vitro or in an extra-corporeal blood circulation. The collimated beam from a lightsource enters a measuring chamber containing the blood sample, at a right angle to the flow direction of the sample. For absorption measurement two photodetectors are employed, the first being oriented in the direction of the incident light (transmitted radiation), while the second is positioned at a distance from this central direction (scattered radiation). The radiation components picked up by this second detector are strongly influenced by the sodium concentration, thus permitting its quantitative determination.
Since the intensity of transmitted radiation is by far greater than that of scattered radiation (by a factor 100), a disadvantageous influence on the scattered light detector by the measurement radiation cannot be avoided in the known measurement systems. At least part of the primary measurement radiation may enter the scattered light detector via scattering or reflection processes outside the sample or directly and may thus invalidate measurement results.
It is the object of the present invention to further develop a measuring system as described above in such a way that a relevant measurement signal which is not influenced by primary radiation, may be picked up by the scattered light detector.
The invention attains this by positioning the first detector and the second detector on different sides of a plane which contains the capillary axis and is at a right angle with the axis of the measurement beam. Scattered radiation is thus measured in a back scatter position, which is novel compared with the state of the art and ensures that an influence of the primary measurement radiation on the scattered light detector is avoided simply by the geometry of the set up. By this means the intensity for the zero value measurement (capillary filled with pure water) may be kept very low, which will result in a large analytic measurement range. When a real sample is measured the measurement radiation interacts with the scattering particles of the sample and is partly absorbed and partly scattered independently of direction. Part of the scattered light propagates in the direction of the second detector (the scattered light detector), another part arrives at the wall of the capillary or enters this wall, which acts as a light guide and again introduces a part of this light into the sample, where it is subject to further scattering. Thus the measurement radiation may propagate over a relatively long interaction zone in the direction of the scattered light detector, where it is picked up as scattered radiation by the second detector placed at a right angle to the capillary axis. In a preferred variant of the invention the optical axis of the second detector is oriented essentially parallel to the axis of the beam of measurement radiation. Although even considerable deviations from the parallel alignment (+/xe2x88x9280xc2x0) will still produce useable results, as long as the scattered light detector is positioned in a back-scatter geometry, the best results will of course be obtained in the 0xc2x0-position (see embodiment in FIG. 4).
Optical conductivity of the capillary wall is provided in a variant of the invention by an optically thinner medium (e.g. air) on the outside of the capillary wall. If the capillary is placed in the bore of a measurement block, the invention prescribes that between the input region of the measurement radiation and the output region of the scattered radiation be placed at least one optical separating element, which covers the annular gap between the capillary and the wall of the bore. This will prevent parts of the measurement radiation from reaching the second detector by reflexion or mirror effects or scattering in air on the outside of the capillary.
It is of particular advantage in this respect to configure the optical separating element as an 0-ring or as a ring with square cross-section which will center the capillary in the bore of the measurement block.
It has furthermore been found that the signal quality of the scattered light detector can be improved if the bore of the measurement block has a diffusely reflecting surface at least between the input region of the measurement radiation and the output region of the scattered radiation.
In another advantageous variant of the invention it is provided that the exterior wall of the capillary, except the input region of the measurement radiation and the output region of the scattered radiation, is mirror-coated or coated with a dichroic layer.